10. Cardiac Arrhythmias - Robert B. Parker, PharmD, FCCP


Cardiac arrhythmias are abnormal heart rhythms resulting from alterations in impulse formation or conduction.

10-1. Electrophysiology

Impulse Generation (Automaticity) and Conduction

• Initiation and propagation of the electrical impulse in cardiac cells is dependent on regulation of the action potential.

• Conduction velocity is determined by regulation of action potential, specifically the slope of phase 0 depolarization (

Figure 10-1 and

Table 10-1).

• The absolute refractory period is the time during which cardiac cells cannot conduct or propagate an action potential (Figure 10-1 and Table 10-1).

• The relative refractory period is the time during which cardiac cells may conduct and propagate action potentials secondary to strong electrical stimuli.

Normal Conduction System

The sinoatrial (SA) node, located in the right atrium, initiates an impulse that

• Stimulates the left atrium and atrioventricular (AV) node, which

• Stimulates the left and right bundle branches via the bundle of His, which then

• Stimulates Purkinje fibers and causes ventricular contraction

10-2. Mechanisms of Arrhythmia

Cardiac arrhythmias arise secondary to the following disorders:

• Automaticity (impulse generation)

• Latent pacemaker (non-SA node pacemaker)

• Triggered automaticity (early or late after-depolarizations)

• Reentry

• Impulse conduction

• Automaticity and impulse conduction

10-3. Clinical Manifestations


Symptoms associated with ventricular arrhythmias range from asymptomatic to loss of consciousness and death. Patients with ventricular tachycardia (VT) may be asymptomatic, but VT can result in hypotension, syncope, or death. Ventricular fibrillation (VF) produces no cardiac output and causes most cases of sudden cardiac death.

Symptoms generally related to poor cardiac output include dizziness, syncope, chest pain, fatigue, confusion, and exacerbation of heart failure. Patients with tachyarrhythmias may report palpitations. With atrial fibrillation or flutter, patients may also experience dizziness, palpitations, light-headedness, and dyspnea

[Figure 10-1. Action Potential for Atrial and Ventricular Tissue]

as well as symptoms of transient ischemic attack (TIA) or stroke.


• Electrocardiogram (ECG) abnormalities may present.

• Ventricular rate can be assessed by documenting the heart rate from the radial artery or by carotid palpation.

10-4. Diagnostic Criteria and Therapy According to Arrhythmia Classification


Arrhythmias are defined by

• Anatomic location

• Supraventricular arrhythmias arise from abnormalities in the SA node, the atrial tissue, the AV node, or the bundle of His.

[Table 10-1. Phases of Atrial and Ventricular Tissue Action Potential]

• Ventricular arrhythmias originate from below the bundle of His.

• Ventricular rate

• Bradyarrhythmias: Heart rate < 60 beats per minute (bpm).

• Tachyarrhythmias: Heart rate > 100 bpm.


Sinus bradycardia

Diagnostic criteria and characteristics

Heart rate is less than 60 bpm; otherwise, the ECG is normal.

Mechanism of arrhythmia

The mechanism of arrhythmia is decreased SA node automaticity.

Clinical etiology

Causes include acute myocardial infarction; hypothyroidism; drug-induced causes (β-blockers including ophthalmic agents, digoxin, calcium channel blockers [diltiazem, verapamil], clonidine, amiodarone, and cholinergic agents); and hyperkalemia

Treatment goals

Restore normal sinus rhythm if the patient is clinically symptomatic.

Drug and nondrug therapy

For intermittent symptomatic episodes: give atropine 0.5-1.0 mg intravenously repeated up to maximum dose of 3.0 mg.

For persistent episodes or if there is no response to atropine: place transvenous or transcutaneous pacemaker.

Atrioventricular block

Diagnostic criteria and characteristics

Criteria are as follows:

• First-degree: Prolonged PR interval > 0.20 seconds, 1:1 atrioventricular conduction

• Second-degree Mobitz type I: Gradual prolongation of PR interval followed by P wave without ventricular conduction

• Second-degree Mobitz type II: Constant PR interval with intermittent P wave without ventricular conduction; may have widened QRS complex

• Third-degree: Heart rate 30-60 bpm; no temporal relation between atrial and ventricular contraction; ventricular contraction initiated by AV junction or ventricular tissue

Mechanism of arrhythmia

The mechanism of arrhythmia is prolonged conduction.

Clinical etiology

Causes include AV nodal disease; acute myocardial infarction; myocarditis; increased vagal tone; drug-induced causes (β-blockers, digoxin, calcium channel blockers [diltiazem and verapamil]; clonidine, amiodarone, cholinergic agents); and hyperkalemia.

Treatment goals

Restore sinus rhythm if the patient is symptomatic

Drug and nondrug therapy

If the cause is reversible, treat with a temporary pacemaker or intermittent atropine.

If the condition is chronic, implant a permanent pacemaker.

Supraventricular Arrhythmias

Atrial fibrillation and atrial flutter

Diagnostic criteria and characteristics

Criteria are as follows:

• Atrial Fibrillation: No P waves; irregularly irregular QRS pattern

• Atrial Flutter: Sawtooth P wave pattern; regular QRS pattern

• Ventricular response: Usually fast but can also be slow or normal

Mechanism of arrhythmia

The mechanism of arrhythmia is enhanced automaticity and reentrant circuits.

Clinical etiology

Causes include rheumatic heart disease, heart failure, hypertension, ischemic heart disease, pericarditis, cardiomyopathy, mitral valve prolapse, cardiac surgery, infection, alcohol abuse, hyperthyroidism, chronic obstructive pulmonary disease, pulmonary embolism, and idiopathic causes (lone atrial fibrillation).

Atrial fibrillation and flutter are the most commonly occurring arrhythmia, and risk increases with age.

Complications include stroke, heart failure exacerbation.

Specific treatment goals for atrial fibrillation

Figure 10-2 illustrates the treatment algorithm for atrial fibrillation.

Control the ventricular rate

Digoxin is the drug of first choice in patients with left ventricular systolic dysfunction (e.g., left ventricular ejection fraction < 40%); it slows the ventricular rate but has poor control in hyperadrenergic-induced atrial fibrillation.

The most effective agents are β-blockers (esmolol, metoprolol, propranolol, others).

Calcium channel blockers (diltiazem, verapamil) may be used but should be avoided in patients with left ventricular systolic dysfunction.

For rapid control of ventricular rate, the intravenous (IV) route of administration should be used.

Digoxin, calcium channel blockers, and β-blockers do not restore sinus rhythm.

Restore and maintain sinus rhythm

Acute conversion to sinus rhythm may be required in patients with atrial fibrillation who are hemodynamically unstable (e.g., hypotensive).

Restoration of sinus rhythm is usually accomplished by electrical cardioversion or administration of antiarrhythmic drugs (AADs).

An important area of controversy centers on whether chronic AAD therapy should be administered to maintain sinus rhythm after cardioversion (rhythm control approach) or whether patients should simply be treated with agents to control ventricular response and anticoagulants to prevent thromboembolic stroke (rate control approach).

Historically, AADs were frequently used to restore and maintain sinus rhythm in patients with atrial fibrillation (rhythm control approach). With chronic therapy, AADs approximately double the chances of a patient remaining in sinus rhythm. However, this approach exposes patients to the large number of adverse effects associated with AADs. The rationale for this approach includes the possibility of fewer symptoms, lower risk of stroke, improved quality of life, and reduced mortality. However, these benefits had never been proven in large clinical trials.

The alternative approach, so called rate control, involves using drugs to control the ventricular response and chronic anticoagulation, usually with warfarin, for stroke prevention.

The rate control and rhythm control approaches have recently been compared in a number of large clinical trials, and the studies demonstrate no advantage for rhythm control over the rate control approach. Regardless of the approach, adequate anticoagulation is needed to prevent stroke.

Even when chronic antiarrhythmic therapy is used to maintain sinus rhythm, it is not 100% effective. Therefore, this approach is usually reserved for patients with recurrent, symptomatic episodes.

Prevent thromboembolism

Prior to use of pharmacologic or direct-current cardioversion: If atrial fibrillation is present for ≥ 48 hours or of unknown duration, anticoagulate with warfarin (INR [international normalized ratio] 2-3) for 3 weeks prior to elective cardioversion, and continue for at least 4 weeks after sinus rhythm has been restored.

If atrial fibrillation is present for ≥ 48 hours or of unknown duration, transesophageal echocardiography (TEE) is often used to determine the presence of atrial thrombus. If no thrombus is seen, cardioversion can be attempted after initiation of IV unfractionated heparin (aPTT [activated partial thromboplastin time] 50-70 seconds) or low molecular weight heparin (full deep vein thrombosis treatment doses). If cardioversion is successful and sinus rhythm is maintained, patients should receive warfarin (INR 2-3) for at least 4 weeks. If atrial thrombus is seen on TEE, anticoagulation should be initiated and repeat TEE performed before attempting later cardioversion.

Risk factors for nonvalvular atrial fibrillation thromboembolism are as follows:

• Previous ischemic stroke, systemic embolism, or TIA

• History of hypertension

• Moderately or severely impaired left ventricular systolic function, heart failure, or both

• Diabetes mellitus

• Age over 75 years

Recommended antithrombotic therapy

The following treatments are recommended:

• Patients with a prior ischemic stroke, systemic embolism, or TIA should receive warfarin INR 2-3.

• Patients with two or more of the following risk factors should receive warfarin (INR 2-3): (1) age exceeding 75 years; (2) history of hypertension; (3) diabetes; and (4) moderately or severely impaired left ventricular systolic function, heart failure, or both. This treatment corresponds to individuals with a CHADS2 (cardiac failure, hypertension, age, diabetes, stroke [doubled]) score ≥ 2.

[Figure 10-2. Treatment Algorithm for Atrial Fibrillation]

• Patients with only one of the following risk factors should receive warfarin (INR 2-3) or aspirin 75-325 mg daily: (1) age exceeding 75 years; (2) history of hypertension; (3) diabetes; (4) moderately or severely impaired left ventricular systolic function, heart failure, or both.

• Patients with none of the following risk factors should receive aspirin 75-325 mg daily: (1) age > 75 years; (2) history of hypertension; (3) diabetes; (4) moderately or severely impaired left ventricular systolic function, heart failure, or both.

Dosage forms for warfarin (Coumadin) are as follows:

• Tablets: 1 mg (pink), 2 mg (lavender), 2.5 mg (green), 3 mg (tan), 4 mg (blue), 5 mg (peach), 6 mg (teal), 7.5 mg (yellow), 10 mg (white)

• Injections (IV): 5 mg powder for reconstitution (2 mg/mL)

Mechanism of action

Warfarin inhibits vitamin K epoxide-reductase and vitamin K reductase, preventing the conversion of vitamin K epoxide to vitamin K. It ultimately inhibits formation of vitamin K-dependent coagulation factors II, VII, IX, and X, as well as proteins C and S


Bioavailability of warfarin is 80% to 100% following oral administration. It is absorbed in the upper gastrointestinal tract. Food or enteral feedings may decrease rate and extent of absorption.


Warfarin is 99.0% to 99.5% protein bound, primarily to albumin.

Metabolism and elimination

Warfarin is administered as a racemic mixture of S- and R-warfarin; the S-isomer is five times more potent than the R-isomer. The S-isomer is primarily metabolized in the liver via cytochrome P450 2C9 (CYP2C9). The R-isomer is metabolized by several other enzymes of the cytochrome P450 system.

Warfarin has low-extraction pharmacokinetic characteristics.

Clearance decreases with increasing age.

The half-life of the R-isomer is 45 hours; for the S-isomer, it is 33 hours.


Recent studies show that genetic polymorphisms can markedly influence the metabolism and response to warfarin. Mutations in two genes—CYP2C9, which codes for the hepatic enzyme that metabolizes S-warfarin, and VKORC1, which regulates the vitamin K epoxide-reductase enzyme (VKORC1)—can account for up to 50% of the variability in the dose of warfarin. The current package insert contains information regarding altered responses caused by polymorphisms in the CYP2C9 and VKORC1 genes. However, the use of genetic testing to prospectively determine the dose of warfarin remains controversial.


The S-isomer is approximately five times more potent than the R-isomer in inhibiting vitamin K reductase. Its pharmacodynamic effect (change in INR) is an indirect effect of the decreased formation of the vitamin K-dependent coagulation factors II, VII, IX, and X. The long half-lives of these factors result in delayed onset of action and delayed response to dosage changes.

Adverse effects

Several adverse effects are possible:

• Bleeding can occur, roughly proportional to the degree of anticoagulation.

• Skin necrosis, related to depletion of or deficiency of protein C, is possible. This effect usually occurs within 10 days of warfarin initiation. Incidence is low.

• Purple-toe syndrome may occur. This syndrome usually occurs 3-8 weeks after warfarin initiation. Incidence is low.

• Birth defects and fetal hemorrhage are possible. Therefore, warfarin is pregnancy category X.

Some common drug interactions

Medications decreasing warfarin anticoagulant response are as follows:

• Barbiturates

• Carbamazepine

• Cholestyramine

• Griseofulvin

• Nafcillin

• Phenytoin (chronic therapy)

• Rifampin

Medications increasing warfarin anticoagulant response are as follows:

• Acetaminophen

• Allopurinol

• Amiodarone

• Azole antifungal agents

• Cimetidine

• Ciprofloxacin, levofloxacin

• Diltiazem

• Erythromycin, clarithromycin

• Fenofibrate

• Fish oil

• Metronidazole

• Omeprazole (R-enantiomer)

• Phenytoin (acute therapy)

• Propafenone

• Simvastatin, fluvastatin

• Sulfinpyrazone

• Trimethoprim-sulfamethoxazole

Dosing management

Patients should take a once-daily dose of 1-10 mg orally. Patient response is highly variable. Management of elevated INR is described in

Table 10-2.


The standard for assessing the degree of anticoagulation is the INR = (observed prothrombin ratio)ISI, where ISI is the International Standardized Index, which corrects for variability in thromboplastin sensitivity.

Initially, the INR is monitored every 1-2 days until the desired INR is achieved and has stabilized at a given dose. Periodic INR monitoring (i.e., monthly) is recommended thereafter unless dosage changes are made.

Paroxysmal supraventricular tachycardia

Diagnostic criteria and characteristics

Criteria for paroxysmal supraventricular tachycardia (PSVT) are as follows:

• Heart rate of 160-240 bpm that is abrupt in onset and termination with a normal QRS interval

• 1:1 AV conduction

Mechanism of arrhythmia

The mechanism of arrhythmia is reentry.

Clinical etiology

Causes include idiopathic causes, fever, and drug-induced causes (sympathomimetics, anticholinergics, β-agonists).

Treatment goals


Figure 10-3 for the treatment algorithm for PSVT. Treatment goals are as follows:

• Acute: Terminate reentry circuit by prolonging refractoriness and slowing conduction.

• Chronic: Prevent or minimize the number and severity of episodes. Antiarrhythmic drugs are no longer the treatment of choice to prevent recurrences. Most patients undergo radiofrequency catheter ablation of the reentrant substrate, which is curative and is associated with a low complication rate.

Acute nonpharmacologic therapy

Vagal maneuvers may terminate PSVT: carotid massage and Valsalva maneuver (most common), squatting, deep breathing, coughing, inducing eyeball pressure, and diving reflex (less common).

Ventricular Arrhythmias

Major classifications and diagnostic criteria

• Premature ventricular contractions

• Premature ventricular contractions (PVCs) are extra abnormal heartbeats that originate in the

[Table 10-2. Management of Elevated International Normalized Ratio]

[Figure 10-3. Treatment Algorithm for Paroxysmal Supraventricular Tachycardia]

   ventricles. They are termed premature because they occur before the normal heartbeat.

• PVCs often are asymptomatic or cause only mild palpitations.

• Ventricular tachycardia

• Ventricular tachycardia (VT) is defined as three or more consecutive PVCs at a rate exceeding 100 bpm and a wide QRS interval (> 0.12 seconds), usually with a regular pattern.

• Nonsustained VT (NSVT) is defined as an episode that lasts less than 30 seconds.

• Sustained VT is defined as an episode lasts more than 30 seconds.

• Ventricular fibrillation

• Ventricular fibrillation is defined as an absence of organized cardiac electrical or mechanical activity and no recognizable P waves, QRS complexes, or T waves on the ECG.

• Ventricular fibrillation rapidly results in no effective cardiac output, blood pressure, or pulse.

Clinical etiology

Causes include acute myocardial infarction, electrolyte disturbances, catecholamines, and drug-induced causes.

Treatment goals

• Treat acute symptoms precipitating causes

• Restore sinus rhythm

• Prevent/minimize recurrences

10-5. Drug and Nondrug Therapy

Premature Ventricular Contractions

Apparently healthy patients without underlying structural heart disease are not at increased risk for VT or sudden cardiac death; therefore, no drug therapy is necessary.

Patients with PVCs and underlying heart disease (e.g., previous myocardial infarction) are at increased risk for more serious arrhythmias. However, AADs do not reduce this risk, and in fact, their use is associated with increased risk of lethal arrhythmias. All such patients should receive medications proven to improve survival, including β-blockers, antiplatelet agents, statins, ACE inhibitors, and aldosterone antagonists if appropriate. An implantable cardioverter defibrillator (ICD) is indicated in such patients with a left ventricular ejection fraction (LVEF) ≤ 30-40% to reduce mortality.

Nonsustained Ventricular Tachycardia

For patients with heart disease and LVEF > 40%, Maximize other cardiovascular medications with proven effects on survival (see previous paragraph).

For patients with heart disease and LVEF ≤ 30% to 40%, recent studies indicate that they are at increased risk for sudden cardiac death (usually from ventricular fibrillation). Use of an ICD improves survival in this group, whereas amiodarone does not affect survival. Even in the absence of PVCs or NSVT in this patient group, these patients are at increased risk for sudden cardiac death, and an ICD is indicated to improve survival.

Unless contraindicated, these patients should also receive standard background therapy, which includes aspirin, ACE inhibitors, β-blockers, statins, and aldosterone antagonists.

Sustained Ventricular Tachycardia or Ventricular Fibrillation (Postresuscitation)

If the event occurs within 24-48 hours of myocardial infarction or because of other reversible causes, no antiarrhythmic drug therapy is needed except β-blockers.

If the event is not secondary to myocardial infarction or another reversible cause, ICD placement is recommended.

Antiarrhythmic drugs (i.e., amiodarone) may still be required to decrease the number of defibrillator discharges, increase patient comfort, and prolong battery life.

Amiodarone can be considered if the patient refuses ICD placement.

Torsades de Pointes

This is a specific variety of ventricular tachycardia with QRS complexes that appear to twist around the ECG baseline. It is associated with a prolonged QT interval.

Clinical etiology

Causes are as follows:

• Genetic abnormalities in cardiac potassium channels

• Acquired

• Hypokalemia, hypomagnesemia

• Myocardial ischemia or infarction

• Subarachnoid hemorrhage

• Hypothyroidism

• Myocarditis or cardiomyopathy

• Arsenic poisoning

• Drug-induced causes (known association with torsades de pointes)

• Antiarrhythmics: Quinidine, procainamide, disopyramide, sotalol, ibutilide, dofetilide, amiodarone

• Antipsychotics: Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, atypical antipsychotics (e.g., quetiapine, ziprasidone)

• Antidepressants: amitriptyline, desipramine, doxepin, imipramine, nortriptyline

• Antibiotics: erythromycin, clarithromycin, gatifloxacin, moxifloxacin, sparfloxacin, pentamidine, trimethoprim-sulfamethoxazole

• Others: methadone, droperidol


• Stop the offending drug if possible.

• Administer direct-current cardioversion for hemodynamically unstable patients.

• Administer magnesium sulfate 2 g over 1 minute IV.

• Use a pacemaker or isoproterenol infusion to increase heart rate.

• Correct hypokalemia or hypomagnesemia.

Drug therapy


Tables 10-3,

10-4, and

10-5 for information about antiarrhythmic drugs. Antiarrhythmic drugs terminate or minimize arrhythmias by

[Table 10-3. Effects of Antiarrhythmic Drugs on Cardiac Electrophysiology]

• Decreasing automaticity of abnormal pacemaker tissues

• Altering conduction characteristics of reentry

• Increasing refractory period

• Eliminating premature impulses that trigger reentry

Patient counseling

Patients should be counseled to take medication as prescribed. If a dose is missed, have the patient take the dose as soon as it is remembered, unless close to the next scheduled dose. In this case, the patient should skip the missed dose and continue the regular regimen; doses should not be doubled.

Many drug interactions are possible. Patients should inform health care providers of medications prescribed prior to starting new medications, including over-the-counter medications (

Table 10-6).

Periodic ECG and laboratory assessments may be required to minimize or prevent adverse effects.

Patients should be educated that complete remission of their arrhythmia is unlikely. However, symptomatic arrhythmias that have increased in frequency or severity should be reported to the physician immediately.

Patients with atrial fibrillation or flutter should be educated about the importance of antithrombotic therapy as well as the signs and symptoms of stroke. Patients with symptoms including sudden onset of slurred speech, facial drooping, or muscle weakness should seek emergent care.

Antiarrhythmic drugs that are administered as extended-release formulations should not be crushed, opened, or chewed. Advise patients to swallow the dose whole.

Drug-specific information


The U.S. Food and Drug Administration now requires that a medication guide be distributed directly to each patient to whom amiodarone is dispensed.

Visual disturbances are rare but should be reported immediately to the physician.

Difficulty breathing, shortness of breath, wheezing, or persistent cough should be reported immediately to the physician.

If the patient experiences nausea or vomiting, passes brown or dark-colored urine, feels more tired than usual, or experiences stomach pain, or if the patient's skin or whites of the eyes turn yellow, the symptoms should be reported immediately to the physician.

Cardiac symptoms such as pounding heart, skipping a beat, or very rapid or slow heartbeats, as well as lightheadedness or feeling faint, should be reported immediately to the physician.

Periodic laboratory tests to evaluate thyroid function, liver function, and pulmonary function, as well as diagnostic tests such as chest x-ray, ECG, and eye exams may be necessary to assess and prevent adverse events (

Table 10-7).

Amiodarone may cause skin photosensitivity. Patients should be advised to wear protective clothing and sunscreen when exposed to sunlight or ultraviolet light.

Prolonged use may cause blue-gray skin discoloration.

Patients should tell their doctor and pharmacist about all other medicines they take, including prescription and nonprescription medicine, vitamins, and herbal supplements.

Frequent administration with grapefruit juice may increase oral absorption. Encourage patients to drink water with amiodarone or separate grapefruit juice consumption by at least 2 hours.

β-blockers (including sotalol)

Patients with asthma and chronic obstructive pulmonary disease should be advised that β-blockers may worsen their symptoms of airway disease. Advise patients to notify physician immediately if this occurs.

Patients with diabetes should be advised that β-blockers may mask symptoms of hypoglycemia.

Patients should avoid abrupt withdrawal of β-blocker therapy. If withdrawal of β-blocker therapy is desired, the patient should contact the physician for the dosage-tapering regimen, if necessary.


Refer to chapter 9.

[Table 10-4. Antiarrhythmic Drug Availability and Standard Dosing Regimens]

[Table 10-5. Pharmacokinetics of Antiarrhythmic Drugs]

[Table 10-6. Antiarrhythmic Drug Interactions and Significant Adverse Effects]

[Table 10-7. Suggested Monitoring Guidelines for Amiodarone]


Warfarin should be avoided at any time during pregnancy.

To determine the correct dosage, the physician may need to check the patient's INR regularly.

Encourage patients to maintain consistency in their diet. Abrupt changes, particularly in the intake of green leafy vegetables, may alter the effectiveness of warfarin.

Minor cuts may take longer to stop bleeding. If a cut or injury fails to stop bleeding, patients should be advised to contact their health care provider.

Excessive alcohol intake may alter the effectiveness of this medication.

Patients should tell their doctor and pharmacist about all other medicines they take, including prescription and nonprescription medicine, vitamins, and herbal supplements.

10-6. Key Points

• All antiarrhythmic drugs are proarrhythmic.

• Cardiac arrhythmias range from benign to lethal.

• Antiarrhythmic drug therapy should be individualized to patient response while minimizing adverse effects.

• Most antiarrhythmic drugs are hepatically eliminated and are associated with significant drug interactions.

• Nonpharmacologic therapy is an important treatment modality, particularly for life-threatening ventricular tachycardia and ventricular fibrillation.

• Treatment of atrial fibrillation should always include an assessment of antithrombotic therapy.

• Direct-current cardioversion is typically the treatment of choice for severely symptomatic arrhythmias.

• Anticoagulant response to warfarin therapy is influenced by numerous factors, including diet, drug interactions, genetics, and concomitant diseases.

• The treatment of excessive anticoagulation secondary to warfarin should be based on the INR, the presence of active bleeding, and the risk of recurrent thromboembolism.

• Patient education and appropriate monitoring are important aspects of successful therapy that can minimize adverse effects.

10-7. Questions


Which of the following is (are) adverse effect(s) of orally administered amiodarone?

I. Photosensitivity

II. Pulmonary fibrosis

III. Phlebitis

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III



Which of the following antiarrhythmic agents' mechanism of action is primarily the result of sodium ion transport blockade?

A. Propafenone

B. Ibutilide

C. Sotalol

D. Verapamil

E. Diltiazem



First-degree atrioventricular heart block can be categorized as a disorder of

I. automaticity.

II. reentry.

III. conduction.

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III



Each of the following can be symptoms of atrial fibrillation except

A. dizziness.

B. palpitations.

C. angina.

D. hypertension.

E. sudden-onset slurred speech.



Each of the following is recommended for monitoring patients requiring chronic amiodarone therapy except

A. electrocardiogram.

B. coagulation tests.

C. thyroid function tests.

D. liver function tests.

E. chest x-ray.



For the treatment of chronic atrial fibrillation, each of the following patients should receive long-term warfarin therapy with a target INR 2.0-3.0 except for

A. patients with heart failure and diabetes.

B. patients over 75 years old with hypertension.

C. a 50-year-old male with no risk factors for thromboembolism.

D. a 77-year-old female with diabetes and hypertension.

E. a 63-year-old male who has had a previous stroke.



Patients with which type of arrhythmia should be educated on performing vagal maneuvers to restore sinus rhythm?

A. Paroxysmal supraventricular tachycardia

B. Torsades de pointes

C. Atrial flutter

D. Sinus bradycardia

E. Ventricular fibrillation



Which of the following medications would be preferred for control of ventricular response in patients with atrial fibrillation and heart failure?

A. Digoxin

B. Verapamil

C. Diltiazem

D. Amlodipine

E. Dofetilide



Which of the following medications is (are) associated with torsades de pointes?

I. Dofetilide

II. Droperidol

III. Erythromycin

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III



Which of the following are important determinants of the pharmacokinetics and response to warfarin?

I. CYP2C9 genotype

II. CYP2D6 genotype

III. VKORC1 genotype

A. I only

B. II only

C. I and II only

D. I, II, and III

E. I and III only



What is the recommended dosage regimen for dofetilide in a patient with a calculated creatinine clearance of 30 mL per minute?

A. Dofetilide therapy not recommended.

B. 125 mcg PO bid

C. 125 mg PO bid

D. 500 mcg PO bid

E. 500 mg PO bid



Sotalol is metabolized by and inhibits the metabolism of which cytochrome P450 enzymes, respectively?

A. CYP3A4 and CYP2D6

B. CYP2D6 and CYP3A4

C. P-gp and CYP2D6

D. P-gp and CYP3A4

E. None of the above



Which of the following antiarrhythmic agents does not increase digoxin concentrations when used concomitantly?

A. Quinidine

B. Dofetilide

C. Amiodarone

D. Diltiazem

E. Verapamil



A 66-year-old male with a past medical history of congestive heart failure and hypertension is receiving lisinopril 10 mg PO qd, digoxin 0.25 mg PO qd, carvedilol 25 mg bid, and spironolactone 25 mg PO qd at home. He now presents to the emergency room with a 1-week history of intermittent palpitations and dizziness. The ECG reveals atrial fibrillation with a ventricular rate of 130 bpm. The decision is made to attempt to restore normal sinus rhythm. Which of the following represents the best therapeutic approach to cardioverting the patient?

A. Perform transesophageal echocardiography; if no thrombus is present, cardiovert; no need for anticoagulation.

B. Perform transesophageal echocardiography; if no thrombus is present, cardiovert; anticoagulate for at least 4 weeks postcardioversion.

C. Anticoagulate for 4 weeks prior to cardioversion; discontinue anticoagulation postcardioversion.

D. Anticoagulate for 2 weeks prior to cardioversion; continue anticoagulation for at least 4 weeks postcardioversion.

E. Direct-current cardiovert immediately.



After the initial successful cardioversion, the patient in the previous question continues to have recurrent symptomatic atrial fibrillation episodes. Chronic therapy to maintain sinus rhythm is to be initiated. Which of the following antiarrhythmic drugs would be the best choice to maintain sinus rhythm?

A. Flecainide

B. Amiodarone

C. Sotalol

D. Ibutilide

E. Digoxin



In a patient with mildly symptomatic paroxysmal supraventricular tachycardia, verapamil should be used for which rhythm(s)?

I. Narrow QRS complex, regular interval

II. Wide QRS complex, regular interval

III. Wide QRS complex, irregular interval

A. I only

B. III only

C. I and II only

D. II and III only

E. I, II, and III



A 53-year-old male has a past medical history of myocardial infarction and hypertension. He presents to his doctor complaining of short (about 10 seconds in duration), intermittent palpitations during the past 2 days. Tests rule out an acute myocardial infarction, and an echocardiogram shows a left ventricular ejection fraction of 25%. The patient is sent home with a Holter monitor to identify any arrhythmias. The Holter monitor reveals episodes of PVCs and nonsustained ventricular tachycardia. What is the most appropriate intervention for this patient?

A. No therapy is indicated.

B. Place an implantable cardioverter defibrillator (ICD).

C. Start propafenone.

D. Start verapamil.

E. Use direct-current cardioversion.



Treatment of torsades de pointes may include all of the following except

A. discontinuing any drugs associated with prolonged QT interval.

B. isoproterenol infusion.

C. adenosine.

D. magnesium sulfate.

E. atrial-ventricular pacing.



Which of the following antiarrhythmic agents requires dosage adjustment in patients with impaired renal function?

A. Digoxin

B. Amiodarone

C. Lidocaine

D. Verapamil

E. Propafenone



Which of the following is not a characteristic of atrial fibrillation?

A. No discernable P waves

B. Ventricular rate of 100-130 bpm

C. Regular QRS pattern

D. Narrow QRS complex

E. Chaotic atrial contractions



Which of the following would be the best choice for ventricular rate control in atrial fibrillation secondary to hyperthyroidism?

A. Adenosine

B. Digoxin

C. Verapamil

D. Propranolol

E. Atropine



A dose-limiting adverse effect of sotalol is

A. bradycardia.

B. polyneuropathy.

C. metallic taste.

D. agranulocytosis.

E. lupus-like syndrome.



Which of the following is not available in both intravenous and oral dosage forms?

A. Metoprolol

B. Amiodarone

C. Verapamil

D. Digoxin

E. Ibutilide



Dosage adjustment should be considered when warfarin is administered with the following drugs, except for

A. amiodarone.

B. sotalol.

C. quinidine.

D. propafenone.

E. diltiazem.


10-8. Answers


C. Photosensitivity is a common adverse effect of oral amiodarone. Patients should be counseled to limit sun exposure and use sunscreen. Pulmonary fibrosis occurs during prolonged therapy. Phlebitis would be expected to occur only during intravenous amiodarone infusion, particularly through a peripheral intravenous line. A central line is preferred to decrease risk of phlebitis.



A. Propafenone blocks sodium entry into the cardiac cell, slowing depolarization. Ibutilide and sotalol act primarily by blocking potassium transport, whereas verapamil and diltiazem inhibit the calcium channel.



B. Atrioventricular heart block is caused by slowed conduction through the atrioventricular node.



D. Because of loss of functional atrial contraction and rapid ventricular rate (producing palpitations), cardiac output may decrease, resulting in decreased perfusion of major organs, particularly the brain (dizziness, confusion, etc.) and heart (angina and heart failure exacerbation). Depending on the vascular tone, blood pressure may remain stable or fall as a direct result of decreased cardiac output; however, hypertension would not be expected. Patients with atrial fibrillation are at increased risk of thrombosis, particularly stroke, secondary to pooling of blood in the left atrium and subsequent thrombus formation.



B. See Table 10-7 for recommended monitoring parameters and schedule. Coagulation tests are not routinely recommended for patients receiving amiodarone therapy. Coagulation tests may be required if a patient develops severe hepatotoxicity secondary to amiodarone or simply requires concomitant warfarin therapy for atrial fibrillation.



C. Patients under age 75 with no thromboembolic risk factors are at low risk of stroke and should be treated with aspirin 75-325 mg daily rather than warfarin.



A. Vagal maneuvers are effective nonpharmacologic therapy for PSVT because the reentry impulse circuit exists in the atrioventricular node. Although vagal maneuvers will slow the rate in atrial fibrillation or flutter, they will not terminate the arrhythmia because the reentry circuit is in the atrial tissue. Vagal maneuvers will have no effect on ventricular arrhythmia because the impulse arises from below the AV node.



A. Digoxin would be the drug of first choice because it will help slow the ventricular rate and it does not have negative inotropic effects. Both verapamil and diltiazem are negative inotropes and should not be used in patients with heart failure and low LVEF. Although it is a calcium channel blocker, amlodipine does not affect AV nodal conduction. Dofetilide is used for conversion to and maintenance of sinus rhythm, not rate control.



E. All three medications are associated with torsades de pointes.



E. S-warfarin is primarily metabolized by CYP2C9. The VKORC1 gene determines the activity of the vitamin K epoxide-reductase enzyme, which is the target for warfarin. Together, the CYP2C9 and VKORC1 genotypes account for nearly 50% of the variability in warfarin dose. Warfarin is not affected by mutations in the CYP2D6 gene.



B. Dofetilide is renally eliminated and therefore must be adjusted according to creatinine clearance to decrease the significant risk of torsades de pointes. See Table 10-4.



E. Sotalol is eliminated almost entirely by the kidneys and is not affected by CYP450 enzymes.



B. Dofetilide does not increase digoxin concentrations when used concomitantly.



B. Since the patient appears to have been in atrial fibrillation for 1 week by history, there is a significant risk of thromboembolism during conversion to sinus rhythm. Proper treatment would require at least 3-4 weeks of anticoagulation (warfarin INR 2-3) prior to cardioversion, followed by at least 4 weeks of anticoagulation postcardioversion. Alternatively, a transesophageal echocardiogram can be used to rule out an atrial thrombus, allowing immediate cardioversion. Because the atria will require time to recover normal contractile activity, anticoagulation will be required for at least 4 weeks postconversion.



B. Because the patient has heart failure, the results of the Cardiac Arrhythmia Suppression Trial (CAST) indicate that class Ic agents should be avoided because of increased risk of death. Sotalol may worsen heart failure. Ibutilide is indicated for conversion only, not for maintenance of sinus rhythm. Digoxin will control only the ventricular rate; it will have no effect on maintaining sinus rhythm.



A. A wide QRS complex signifies conduction via an accessory pathway other than the AV node. Because calcium channel blockers prolong conduction in the AV node and not in the accessory pathways, administration of these agents will block the AV node and force impulses to be conducted via the accessory pathways, which have shorter refractory periods. Consequently, the ventricular response will significantly increase.



B. Patients with LVEF ≤ 30-40% and previous myocardial infarction are at increased risk of sudden cardiac death, usually from ventricular fibrillation. Implantation of an ICD in these patients reduces the risk of mortality. Propafenone has negative inotropic effects and may worsen heart failure. The risk of ventricular proarrhythmia is significantly increased if propafenone is used in this patient. Verapamil also would worsen heart failure and not reduce the risk of mortality. Direct-current cardioversion is not indicated because the patient is stable. All standard heart failure medications should be optimized.



C. Adenosine is typically used only to terminate paroxysmal supraventricular tachycardia. Discontinuation of drugs that prolong the QT interval is essential to terminate torsades de pointes and prevent recurrences. Treatment should consist of intravenous magnesium sulfate and electrical pacing. An isoproterenol infusion can be used while waiting for electrical pacing.



A. Digoxin requires dosage adjustment in patients with impaired renal function.



C. Atrial fibrillation represents chaotic atrial activity resulting in no identifiable P wave. Because atrial fibrillation originates above the AV node, the QRS complex is narrow and the ventricular rate is typically greater than 100 bpm.



D. β-blockers are the preferred rate-controlling agent for hyperthyroidism because they inhibit the adrenergic response and decrease thyroid hormone conversion (especially propranolol). Digoxin is not as effective in controlling the ventricular rate related to a hyperadrenergic state (hyperthyroidism).



A. Sotalol possesses significant β-blocking activity, and therefore the patient may experience adverse effects similar to traditional β-blockers.



E. All of these medications except ibutilide are available in both intravenous and oral dosage forms.



B. Warfarin is metabolized by multiple cytochrome P450 isoenzymes, including CYP2C9, CYP1A2, and CYP3A4. Amiodarone inhibits by CYP2C9, CYP1A2, and CYP3A4, quinidine by unknown mechanisms, propafenone by CYP1A2 and CYP3A4, and diltiazem by CYP3A4. Sotalol is primarily renally eliminated and does not result in cytochrome P450-mediated drug interactions.


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